title: Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.
abstract: BACKGROUND
  Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001.
  
  
  METHODS
  Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy.
  
  
  RESULTS
  A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens.
  
  
  CONCLUSIONS
  The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).
authors.affiliation: Departments of Immuno-Gene Therapy and Cancer Vaccine, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan. kageyama@clin.medic.mie-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kageyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wada
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Shugo
authors.initials: S
authors.lastname: Ueda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Sahoko H
authors.initials: SH
authors.lastname: Sugino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Naoko
authors.initials: N
authors.lastname: Imai
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamada
authors.forename: Masaharu
authors.initials: M
authors.lastname: Osako
authors.forename: Mami
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Naozumi
authors.initials: N
authors.lastname: Harada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hishida
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000368:Aged; D000912:Antibodies, Neoplasm / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002784:Cholesterol / Q000276:immunology*; D003710:Demography; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D005936:Glucans / Q000276:immunology*; D006801:Humans; D007109:Immunity; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D005936:Glucans; D008565:Membrane Proteins; D011994:Recombinant Proteins; C009109:pullulan; D002784:Cholesterol